What is the best drug treatment for premenopausal women with bleeding irregularities using the levonorgestrel-releasing intrauterine system? A systematic review.

OBJECTIVE: Up to 60% of women discontinue using the levonorgestrel-releasing intrauterine system (LNG-IUS) within 5 years because of bleeding irregularities, pain and/or systemic progestogenic adverse effects. The aim of the study was to assess treatment options for bleeding irregularities in women using the 52 mg LNG-IUS. METHODS: Database searches of Medline, Embase/Ovid and the Cochrane Library were carried out, and journals were searched by hand, for relevant studies published from database inception to March 2020. Inclusion criteria were randomised controlled trials (RCTs), prospective cohort studies and case-control studies of premenopausal women using the LNG-IUS and receiving medical treatment for bleeding irregularities. Screening, data extraction and quality assessment of retrieved articles were carried out independently by two pairs of reviewers. The primary outcome was the reduction of bleeding/spotting days. RESULTS: Of the 3061 studies identified, eight met our inclusion criteria: six RCTs and two prospective cohort studies. The eight studies enrolled a total of 677 women who were treated with tamoxifen, mifepristone, ulipristal acetate, naproxen, oestradiol, mefenamic acid, tranexamic acid or the progesterone receptor modulator CDB 2914. The results of our analysis indicated that naproxen may be effective for the prophylactic treatment of bleeding immediately (<12 weeks) after LNG-IUS insertion (high level of evidence). Oestradiol may be effective in treating ongoing bleeding irregularities >6 months after insertion (low level of evidence). CONCLUSION: Evidence for the medical treatment of (ongoing) bleeding irregularities during use of the LNG-IUS is lacking and more research is needed on the topic.

The impact of embedment of the side arms of 52 mg levonorgestrel-intrauterine device on bleeding and pain: A prospective cohort study.

PURPOSE: The purpose of this study was to analyse the impact of embedment of side arms of the levonorgestrel 52 mg intrauterine device (LNG-IUD) in the myometrium (assessed by three-dimensional transvaginal ultrasound (3D-TVUS)) on uterine bleeding and pain. MATERIALS AND METHODS: We performed a prospective cohort study in a large Dutch teaching hospital between February 2015 and December 2016. Participants over 18 years of age who selected a LNG-IUD for contraception or because of heavy menstrual bleeding were eligible for inclusion. Six weeks after insertion, a 3D-TVUS was performed to diagnose embedment of the side arms. At that moment participants filled in questionnaires about their bleeding pattern and pelvic pain. Menstruation patterns 'no bleeding', 'regular menstruation', 'sometimes a day of spotting (maximum once a week)' were classified as favourable bleeding pattern. Menstruation patterns 'heavy menstrual bleeding', 'several days a week bleeding days', 'several days a week spotting days', 'continuously spotting', and 'completely irregular cycle' were classified as unfavourable bleeding pattern. Univariate and multivariate logistic regression analysis was used to calculate odds ratios (OR) and 95 %-confidence intervals (CI). The multivariate analysis included endometrial thickness, reason for insertion and parity. The analysis of pelvic pain additionally included previous insertion. RESULTS: A total of 220 participants were evaluated for the study of whom 176 returned the questionnaires. Embedment of the side arms was observed in 43 of the 176 responding participants (24.4 %). Favourable bleeding pattern was reported by 25/43 (58.1 %) participants with embedment and 53/133 (39.8 %) participants without embedment (ORadj 1.8, 95 % CI 0.9-3.9). Pelvic pain was reported by 4/43 (9.3 %) participants with embedment and 24/133 (18.1 %) participants without embedment (ORadj 0.3; CI 0.1-1.2). CONCLUSIONS: The present study suggests that embedment of the side arms of the LNG-IUD in the myometrium assessed by 3D-TVUS is not associated with a unfavourable bleeding pattern nor pelvic pain six weeks after insertion. From this point of view, we do not recommend to perform standard 3D-TVUS for the purpose of excluding or demonstrating embedment.